title: Unique regulation of adipose triglyceride lipase (ATGL) by perilipin 5, a lipid droplet-associated protein.
abstract: Lipolysis is a critical metabolic pathway contributing to energy homeostasis through degradation of triacylglycerides stored in lipid droplets (LDs), releasing fatty acids. Neutral lipid lipases act at the oil/water interface. In mammalian cells, LD surfaces are coated with one or more members of the perilipin protein family, which serve important functions in regulating lipolysis. We investigated mechanisms by which three perilipin proteins control lipolysis by adipocyte triglyceride lipase (ATGL), a key lipase in adipocytes and non-adipose cells. Using a cell culture model, we examined interactions of ATGL and its co-lipase CGI-58 with perilipin 1 (perilipin A), perilipin 2 (adipose differentiation-related protein), and perilipin 5 (LSDP5) using multiple techniques as follows: anisotropy Forster resonance energy transfer, co-immunoprecipitation, [(32)P]orthophosphate radiolabeling, and measurement of lipolysis. The results show that ATGL interacts with CGI-58 and perilipin 5; the latter is selectively expressed in oxidative tissues. Both proteins independently recruited ATGL to the LD surface, but with opposite effects; interaction of ATGL with CGI-58 increased lipolysis, whereas interaction of ATGL with perilipin 5 decreased lipolysis. In contrast, neither perilipin 1 nor 2 interacted directly with ATGL. Activation of protein kinase A (PKA) increased [(32)P]orthophosphate incorporation into perilipin 5 by 2-fold, whereas neither ATGL nor CGI-58 was labeled under the incubation conditions. Cells expressing both ectopic perilipin 5 and ATGL showed a 3-fold increase in lipolysis following activation of PKA. Our studies establish perilipin 5 as a novel ATGL partner and provide evidence that the protein composition of perilipins at the LD surface regulates lipolytic activity of ATGL.
authors.affiliation: Geriatric Research, Education, and Clinical Center, Baltimore Veterans Affairs Health Care Center, Division of Endocrinology, Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland 21201, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Bell
authors.forename: Urmila
authors.initials: U
authors.lastname: Sreenivasan
authors.forename: Urmilla
authors.initials: U
authors.lastname: Sreenevasan
authors.forename: Hong
authors.initials: H
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Knut
authors.initials: K
authors.lastname: Dalen
authors.forename: Constantine
authors.initials: C
authors.lastname: Londos
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Megan A
authors.initials: MA
authors.lastname: Rizzo
authors.forename: Rosalind
authors.initials: R
authors.lastname: Coleman
authors.forename: Dawei
authors.initials: D
authors.lastname: Gong
authors.forename: Dawn
authors.initials: D
authors.lastname: Brasaemle
authors.forename: Carole
authors.initials: C
authors.lastname: Sztalryd
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins; D006224:Cricetinae; D003412:Cricetulus; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D002352:Carrier Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D008049:Lipase; D000070778:Perilipin-1; D010750:Phosphoproteins; C000602978:PLIN1 protein, human; C000602979:Plin1 protein, mouse; C439972:ABHD5 protein, human; C492986:Abhd5 protein, mouse; C494794:PNPLA2 protein, human; D000217:Acyltransferases; C494445:PNPLA2 protein, mouse